The expression of exogenous DNA in eukaryotic cells permits the study of a broad array of biological topics ranging from the regulation of gene expression to the treatment of disease by gene transfer-based therapies. A number of methods for gene transfer into mammalian cells have evolved. These include in vivo and in vitro infection with cloned retroviral vectors (Shimotohno, K., and Temin, H. M. (1981) Cell 26:67–77; Cone, R. D., and Mulligan, R. C. (1984) Proc. Natl. Acad. Sci. USA 81:6349–6353; Dubensky, T. W., Campbell, B. A., and Villareal, L. P. (1984) Proc. Natl. Acad. Sci. USA 81:7529–7533; Seeger, C., Ganem, D. and Varmus, H. E. (1984) Proc. Natl. Acad. Sci. USA 81:5849–5852), coprecipitation of DNA with calcium phosphate (Chu, G., and Sharp, P. (1981) Gene 13:197–202; Benvenisty, N., and Reshef, L. (1986) Proc. Natl. Acad. Sci. USA 83:9551–9555), encapsulation of DNA in liposomes (Felgner, P. L., and Ringold, G. M. (1989) Nature 337:387–388; Kaneda, Y., Iwai, K., and Uchida, T. (1989) Science 243:375–378), direct injection of plasmid DNA (Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., and Felgner, P. L. (1990) Science 247:1465–1468), DEAE-dextran (McCutchan, J. H., and Pagano, J. S. (1968) J. Natl. Cancer Inst. 41:351–357), electroporation (Neumann, E., Schaefer-Ridder, M., Wang, Y., and Hofschneider, P. H. (1982) EMBO J. 1:841–845; Cann, A. J., Koyanagi, Y., and Chen, I. S. Y. (1988) Oncogene 3:123–128), and DNA-coated particle bombardment of cells and tissues (Yang, N-S., Burkholder, J., Roberts, B., Martinell, B., and McCabe, D. (1990) Proc. Natl. Acad. Sci. USA 87:9568–9572).
Although transfection of numerous cell types with an exogenous nucleic acid molecule containing a gene results in efficient expression of the exogenous gene, primary T lymphocytes, e.g. peripheral blood T lymphocytes obtained from an individual, have been found to be refractory to transfection and expression of exogenous DNA. Primary T lymphocytes also have been found to be refractory to expression of the introduced nucleic acid when first stimulated to proliferate. Thus, a system that allows for efficient introduction of exogenous DNA into primary T cells and expression of the exogenous DNA in the T cell is still needed.